Expression of e-cadherin in high-risk breast cancer.

Purpose: E-cadherin expression is diverse, and differences in patient characteristics may produce variability in expression. Whereas some studies have indicated that downregulation of e-cadherin, associated with loss of cellular adhesiveness, was correlative with poor prognosis and metastasis, other studies have failed to confirm this. The present study uses a highly homogenous population of patients at high-risk for breast cancer, on the basis of ethnic and socio-economic status, to examine the relationship between e-cadherin and other prognostic markers in breast cancer.

Correlation and expression of p53, HER-2, vascular endothelial growth factor (VEGF), and e-cadherin in a high-risk breast-cancer population.

Background: Many genetic traits common to aggressive breast carcinoma have been identified; yet little is known about the interrelationships of such traits during tumor development, especially in women prone to aggressive cancer. This study examined the expression of four biological markers associated with poor prognosis at each stage of breast cancer progression in primary tumors from women of lower economic status and assessed the relationship between these markers.

Methods: Archived primary breast tumors from 77 patients were assessed by immunohistochemical analysis for expression of human epidermal growth receptor 2 (HER-2), p53, vascular endothelial growth factor (VEGF), and e-cadherin, and the relationships between the expressions of these molecules were studied.

Fatal exacerbation of paraneoplastic systemic sclerosis after neoadjuvant chemotherapy in a breast cancer patient.

Paraneoplastic systemic sclerosis (SSc) occurs in about 3%-7% of individuals with SSc. There are reports of accelerated SSc syndromes associated in particular with breast cancer. Further exacerbations of the rheumatic condition may be induced by treatment of the cancer.

Selective serotonin reuptake inhibitor-induced rhabdomyolysis associated with irinotecan.

A 74-year-old man was admitted with rhabdomyolysis after undergoing initial treatment for gastrointestinal cancer with irinotecan. The syndrome partially resolved after the discontinuation of all of his usual medications, including his chronic selective serotonin reuptake inhibitor (SSRI). The rhabdomyolysis was exacerbated upon reinitiation of the SSRI and disappeared when the SSRI was discontinued.

Localization of the iron transport proteins Mobilferrin and DMT-1 in the duodenum: the surprising role of mucin.

There are two pathways for inorganic iron uptake in the intestine, the ferric pathway, mediated by the key protein mobilferrin, and the ferrous pathway, mediated by DMT-1. Previous studies reported that the amount of DMT-1 increased in the intestinal mucosa in iron deficiency and the increase was seen in the apical portion of the villus of the duodenal mucosa. Mobilferrin did not quantitatively increase but became localized at the cell membrane.

Dibenzoylmethane, a natural dietary compound, induces HIF-1 alpha and increases expression of VEGF.

Hypoxia-inducible factor 1 (HIF-1) is the major transcription factor activated during hypoxia. It is composed of HIF-1 alpha and HIF-1 beta subunits. While HIF-1 beta is constitutively expressed, HIF-1 alpha is targeted to proteasome degradation under normoxic conditions.

DMT1: a mammalian transporter for multiple metals.

DMT1 has four names, transports as many as eight metals, may have four or more isoforms and carries out its transport for multiple purposes. This review is a start at sorting out these multiplicities. A G185R mutation results in diminished gastrointestinal iron uptake and decreased endosomal iron exit in microcytic mice and Belgrade rats.

Pathways of iron absorption.

Iron is vital for all living organisms but excess iron can be lethal because it facilitates free radical formation. Thus iron absorption is carefully regulated to maintain an equilibrium between absorption and body loss of iron. In countries where meat is a significant part of the diet, most body iron is derived from dietary heme because heme binds few of the dietary chelators that bind inorganic iron.

Cellular location of proteins related to iron absorption and transport.

K562 erythroleukemia cells and IEC6 rat cells were examined using confocal microscopy and antibodies raised against DMT-1 (Nramp-2, DCT-1), transferrin receptor (CD71), beta(3) integrin (CD61), mobilferrin (calreticulin), and Hephaestin. The cellular location of each of these proteins was identified by immunofluorescence in both saponin-permeabilized and non-permeabilized cells. Fluorescent reactivity was observed on or near the cell surface of each of these proteins, suggesting that they might participate in surface membrane transport of iron.

The ferrireductase paraferritin contains divalent metal transporter as well as mobilferrin.

Inorganic iron can be transported into cells in the absence of transferrin. Ferric iron enters cells utilizing an integrin-mobilferrin-paraferritin pathway, whereas ferrous iron uptake is facilitated by divalent metal transporter-1 (DMT-1). Immunoprecipitation studies using antimobilferrin antibody precipitated the previously described large-molecular-weight protein complex named paraferritin.